RESUMO
BACKGROUND: No randomised controlled trial has ever been done in patients with metastatic phaeochromocytomas and paragangliomas. Preclinical and first clinical evidence suggested beneficial effects of sunitinib. We aimed to evaluate the safety and efficacy of sunitinib in patients with metastatic phaeochromocytomas and paragangliomas. METHODS: FIRSTMAPPP is a multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial done at 14 academic centres across four European countries. Eligible participants were adults (aged ≥18 years) with sporadic or inherited progressive metastatic phaeochromocytomas and paragangliomas. Patients were randomly assigned (1:1) to receive either oral sunitinib (37·5 mg per day) or placebo. Randomisation was stratified according to SDHB status (mutation present vs wild type) and number of previous systemic therapies (0 vs ≥1). Primary endpoint was the rate of progression-free survival at 12 months according to real-time central review (Response Evaluation Criteria in Solid Tumours version 1.1). On the basis of a two-step Simon model, we aimed for the accrual of 78 patients, assuming a 20% improvement of the 12-month progression-free survival rate from 20% to 40%, to conclude that sunitinib is effective. Crossover from the placebo group was allowed. This trial is registered with ClinicalTrials.gov, number NCT01371201, and is closed for enrolment. FINDINGS: From Dec 1, 2011, to Jan 31, 2019, a total of 78 patients with progressive metastatic phaeochromocytomas and paragangliomas were enrolled (39 patients per group). 25 (32%) of 78 patients had germline SDHx variants and 54 (69%) had used previous therapies. The primary endpoint was met, with a 12-month progression-free survival in 14 of 39 patients (36% [90% CI 23-50]) in the sunitinib group. In the placebo group, the 12-month progression-free survival in seven of 39 patients was 19% (90% CI 11-31), validating the hypotheses of our study design. The most frequent grade 3 or 4 adverse events were asthenia (seven [18%] of 39 and one [3%] of 39), hypertension (five [13%] and four [10%]), and back or bone pain (one [3%] and three [8%]) in the sunitinib and placebo groups, respectively. Three deaths occurred in the sunitinib group: these deaths were due to respiratory insufficiency, amyotrophic lateral sclerosis, and rectal bleeding. Only the latter event was considered drug related. Two deaths occurred in the placebo group due to aspiration pneumonia and septic shock. INTERPRETATION: This first randomised trial supports the use of sunitinib as the medical option with the highest level of evidence for anti-tumour efficacy in progressive metastatic phaeochromocytomas and paragangliomas. FUNDING: French Ministry of Health, through the National Institute for Cancer, German Ministry of Education and Research, and the German Research Foundation within the CRC/Transregio 205/2, EU Seventh Framework Programme, and a private donator grant.
Assuntos
Neoplasias das Glândulas Suprarrenais , Hipertensão , Feocromocitoma , Adulto , Humanos , Adolescente , Sunitinibe/uso terapêutico , Feocromocitoma/tratamento farmacológico , Feocromocitoma/etiologia , Intervalo Livre de Progressão , Hipertensão/etiologia , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/etiologia , Método Duplo-Cego , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical therapies, and an initial course of radiation and are characterized by unrelenting growth and/or metastatic dissemination. Two groups of patients with PitNETs were sequenced: a prospective group of patients (n = 66) who consented to sequencing prior to surgery and a retrospective group (n = 26) comprised of aggressive/higher risk PitNETs. A higher mutational burden and fraction of loss of heterozygosity (LOH) was found in the aggressive, treatment-refractory PitNETs compared to the benign tumors (p = 1.3 × 10-10 and p = 8.5 × 10-9, respectively). Within the corticotroph lineage, a characteristic pattern of recurrent chromosomal LOH in 12 specific chromosomes was associated with treatment-refractoriness (occurring in 11 of 14 treatment-refractory versus 1 of 14 benign corticotroph PitNETs, p = 1.7 × 10-4). Across the cohort, a higher fraction of LOH was identified in tumors with TP53 mutations (p = 3.3 × 10-8). A machine learning approach identified loss of heterozygosity as the most predictive variable for aggressive, treatment-refractory behavior, outperforming the most common gene-level alteration, TP53, with an accuracy of 0.88 (95% CI: 0.70-0.96). Aggressive, treatment-refractory PitNETs are characterized by significant aneuploidy due to widespread chromosomal LOH, most prominently in the corticotroph tumors. This LOH predicts treatment-refractoriness with high accuracy and represents a novel biomarker for this poorly defined PitNET category.
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Perda de Heterozigosidade , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Perda de Heterozigosidade/genética , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Retrospectivos , Mutação/genética , Estudos ProspectivosRESUMO
PURPOSE: To investigate the [68Ga]DOTATOC PET radiomic profile of head and neck paragangliomas (HNPGLs) and identify radiomic characteristics useful as predictors of succinate dehydrogenase genes (SDHx) pathogenic variants. METHODS: Sporadic and SDHx HNPGL patients, who underwent [68Ga]DOTATOC PET/CT, were retrospectively included. HNPGLs were analyzed using LIFEx software, and extracted features were harmonized to correct for batch effects and confronted testing for multiple comparison. Stepwise discriminant analysis was conducted to remove redundancy and identify best discriminating features. ROC analysis was used to define optimal cut-offs. Multivariate decision-tree analysis was performed using CHAID method. RESULTS: 34 patients harboring 60 HNPGLs (51 SDHx in 25 patients) were included. Three sporadic and nine SDHx HNPGLs were metastatic. At stepwise discriminant analysis, both GLSZM-Zone Size Non-Uniformity (ZSNU, reflecting tumor heterogeneity) and IB-TLSRE (total lesion somatostatin receptor expression) were independent predictors of genetic status, with 96.4% of lesions and 91.6% of patients correctly classified after cross validation (p < 0.001). Among non-metastatic patients, GLSZM-ZSNU and IB-TLSRE were significantly higher in sporadic than SDHx HNPGLs (p < 0.001). No differences were revealed in metastatic patients. Decision-tree analysis highlights multifocality and IB-TLSRE as useful variables, correctly identifying 6/9 sporadic and 24/25 SDHx patients. Model failed to classify one SDHA and three sporadic patients (2 metastatic). CONCLUSION: Radiomics features GLSZM-ZSNU and IB-TLSRE appear to reflect HNPGLs SDHx status and tumor behavior (metastatic vs. non-metastatic). If validated, especially IB-TLSRE might represent a simple and time-efficient radiomic index for SDHx variants early screening and prediction of tumor behavior in HNPGL cases.
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Neoplasias de Cabeça e Pescoço , Octreotida , Compostos Organometálicos , Paraganglioma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/genética , Feminino , Masculino , Pessoa de Meia-Idade , Paraganglioma/genética , Paraganglioma/diagnóstico por imagem , Octreotida/análogos & derivados , Projetos Piloto , Adulto , Idoso , Estudos Retrospectivos , Succinato Desidrogenase/genética , Processamento de Imagem Assistida por Computador/métodos , RadiômicaRESUMO
Visual dysfunction is a prevalent symptom in patients with non-functioning pituitary macroadenoma (NFPM); the role of OCT in such patients has not been yet determined. This is a prospective longitudinal observational study over a period of 6 years, on 20 patients presenting a radiological compression of the optic chiasma without visual acuity (VA) and visual field (VF) disturbances. The primary endpoint was to evaluate the impact of NFPA on neuro-axonal loss by measuring RNFL thickness using OCT at inclusion (T0), 12 months (T1), 24 months (T2), and 36 months (T3), respectively. The secondary endpoint was to monitor the evolution of OCT over time and assess any relationship between the degree of OCT alteration and the degree of radiological and clinical optic chiasm compression syndrome. Among the 20 patients included, eight (40%) showed an altered RNFL-OCT at diagnosis, while the remaining 12 (60%) showed a normal pattern. During a mean ophthalmologic follow-up of 60 months, 4 patients (20%) presented an asymptomatic reduction of RNFL-OCT thickness although all 20 had a VA/VF stable. To our knowledge, this study represents the first attempt to longitudinally evaluate the natural history and evolution of RNFL-OCT in patients with radiologically asymptomatic chiasmatic compression syndrome. The results do not clearly demonstrate the role of the OCT as an early prognostic factor for visual dysfunction.
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Quiasma Óptico , Neoplasias Hipofisárias , Humanos , Quiasma Óptico/diagnóstico por imagem , Estudos Prospectivos , Estudos Longitudinais , Campos Visuais , Transtornos da Visão/etiologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/diagnóstico por imagemRESUMO
Background and Objectives: Pituitary abscess (PA) is a rare occurrence, representing less than 1% of pituitary lesions, and is defined by the presence of an infected purulent collection within the sella turcica. Pas can be classified as either primary, when the underlying pituitary is normal prior to infection, or secondary, when there is associated a pre-existing sellar pathology (i.e., pituitary adenoma, Rathke's cleft cysts, or craniopharyngioma), with or without a recent history of surgery. Preoperative diagnosis, owing to both non-specific symptoms and imaging features, remains challenging. Treatment options include endonasal trans-sphenoidal pus evacuation, as well as culture and tailored antibiotic therapy. Methods: A retrospective multicenter study, conducted on a prospectively built database over a 20-year period, identified a large series of 84 patients harboring primary sellar abscess. The study aimed to identify crucial clinical and imaging features in order to accelerate appropriate management. Results: The most common clinical presentation was a symptom triad consisting of various degrees of asthenia (75%), visual impairment (71%), and headache (50%). Diagnosis was achieved in 95% of cases peri- or postoperatively. Functional recovery was good for visual disturbances and headache. Pituitary function recovery remained very poor (23%), whereas the preoperative diagnosis represented a protective factor. Conclusions: In light of the high prevalence of pituitary dysfunction following the management of PAs, early diagnosis and treatment might represent a crucial issue. Currently, there are no standard investigations to establish a conclusive preoperative diagnosis; however, new, emerging imaging methods, in particular nuclear imaging modalities, represent a very promising tool, whose potential warrants further investigations.
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Doenças da Hipófise , Neoplasias Hipofisárias , Humanos , Abscesso , Doenças da Hipófise/complicações , Doenças da Hipófise/diagnóstico , Doenças da Hipófise/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Hipófise/patologia , Cefaleia , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION: In patients with ileal neuroendocrine tumours (ileal NETs), head-to-head evaluation of diagnostic performances of 68 Ga-DOTA-peptides and 18 F-fluorodihydroxyphenylalanine (18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) has been performed in only few small patients' cohorts. The aim of this retrospective study was to compare 68 Ga-DOTATOC and 18 F-FDOPA PET/CT for metastatic disease assessment in a homogeneous large series of patients with well-differentiated ileal NETs. METHODS: All patients with ileal NETs who underwent both 18 F-FDOPA and 68 Ga-DOTATOC PET/CT within a 3-month period and no therapeutic change between the two studies were retrospectively included. The detection rates of both modalities were calculated using per-patient, per-region and per-lesion analyses. RESULTS: Forty one patients with ileal NETs were evaluated. 18 F-FDOPA and 68 Ga-DOTATOC showed similar detection rates according to per-patient (97% for both) and per-region analyses (94% for 18 F-FDOPA vs 88% for 68 Ga-DOTATOC, P = .35). For a total of 605 positive lesions, 458 (76%) were detected by both modalities, 122 (20%) exclusively by 18 F-FDOPA PET/CT, and 25 (4%) by 68 Ga-DOTATOC PET/CT only. In a per-lesion analysis, 18 F-FDOPA PET/CT performed better than 68 Ga-DOTATOC PET/CT (overall detection rates of 96% vs 80%; P < .001). 18 F-FDOPA PET/CT detected significantly more metastases than 68 Ga-DOTATOC PET/CT in the liver, peritoneum, abdominal and supra-diaphragmatic lymph nodes. CONCLUSION: 18 F-FDOPA PET/CT seems not inferior than 68 Ga-DOTATOC PET/CT for the delineation of metastatic spread of ileal NETs. Therefore, according to local expertise and technical availability, 18 F-FDOPA should be considered as a valid clinical diagnostic option for exhaustive metastatic assessment in patients with ileal NETs. Obviously, 68 Ga-DOTATOC PET/CT remains mandatory for PRRT assessment. Further comparative studies are needed to determine the optimal approach in various clinical scenarios such as preoperative staging and primary tumour detection.
Assuntos
Tumores Neuroendócrinos , Compostos Organometálicos , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
BACKGROUND: Vasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning symptoms and tumor burden have been poorly described in VIPoma. OBJECTIVE: Describe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma. METHODS: We retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received. RESULTS: Twenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025). CONCLUSIONS: Surgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies.
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Neoplasias Hepáticas , Neoplasias Pancreáticas , Vipoma , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos , Sunitinibe , Vipoma/terapiaRESUMO
OBJECTIVE: To assess the specificity of increased 18 F-dihydroxyphenylalanine (18 F-FDOPA) uptake in patients who underwent PET/CT for suspicion of isolated pancreatic neuroendocrine tumour (pNET). False-positive results mimicking a pNET have been investigated. MATERIAL AND METHODS: Carbidopa-assisted 18 F-FDOPA PET/CT scans performed in patients with suspicion of localized pNET were retrieved. Only patients with a definitive diagnosis were retrospectively included. When available, the histopathological result after pancreatic surgery was the gold standard. In other cases, the diagnosis was based on endoscopic ultrasonography (EUS)/cytology and/or on concordant imaging results of at least two of the following: contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS). RESULTS: Forty-four among 731 patients were selected. Among these, 36 patients (82%) were surgically treated, revealing pNET (n = 28), solid pseudopapillary tumour (SPT) (n = 4), adenocarcinoma (n = 2), serous cystadenomas (n = 1) and solitary fibrous tumour (n = 1) cases. An additional three cases of pNET were diagnosed by EUS/cytology. In the remaining five patients, a consensus was reached on follow-up imaging results: pNET (n = 1), serous cystadenoma (n = 2) and undetermined/no pNET (n = 2). Both specificity and negative predictive value of 18 F-FDOPA PET/CT for localized pNET were 67%. Surprisingly, all four false-positive results were SPTs showing intense 18 F-FDOPA uptake and negative SRS. There was no significant difference in 18 F-FDOPA uptake intensity between PET-positive pNETs and SPTs. CONCLUSION: 18 F-FDOPA PET/CT is not specific for pNET in patients with localized pancreatic lesions. SPT could mimic pNET and should be part of differential diagnosis in such a clinical situation. If these results are confirmed in a broader population, the imaging pattern 18 F-FDOPA PET-positive/SRS-negative lesions might be considered as the imaging phenotype of SPT.
Assuntos
Neoplasias Pancreáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Diagnóstico Diferencial , Di-Hidroxifenilalanina , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
BACKGROUND: This study evaluated the short- and long-term outcomes of synchronous resection of liver metastases (LM) from small bowel neuroendocrine tumors (SB-NET). METHODS: A retrospective review of patients undergoing resection for LMs from SB-NETs from January 1997 and December 2018 was performed. RESULTS: There were 44 patients with synchronous SB-NET and LMs. Perioperative and 90-day mortality values were zero, and the morbidity rate was 27%. The median overall survival (OS) was 128.4 months (CI 95% 74.0-161.5 months) with 1-, 3-, 5-, and 10-year survival rates of 100%, 83%, 79%, and 60%, respectively. Not achieving surgical treatment for LM was the unique independent factor for survival (HR 6.50; CI 95% 1.54-27.28; p = 0.01) in patients with unresected LMs having OS and 10-year survival rates (42 months, 33%) versus patients undergoing liver resection (152 months, 66%)(p = 0.0008). The recurrence rate was 81.8% and associated with longer OS and 5-year survival rates when limited to the liver [223 months (61%) vs 94 months (87%)]. CONCLUSIONS: Simultaneous resection of SB-NETs with synchronous LMs was safe and associated with considerable long-term survival even in the presence of bilobar disease. However, recurrence after resection was common (81%) but associated with longer survival rates when limited to the liver.
Assuntos
Hepatectomia/métodos , Neoplasias Intestinais/patologia , Intestino Delgado/cirurgia , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: The primary endpoint was to analyze the predictive factors of lymph node involvement (LN+). BACKGROUND: Indications for additional right hemicolectomy (RHC) with lymph node (LN) resection after appendectomy for appendix neuroendocrine tumor (A-NET) remain controversial, especially for tumors between 1 and 2âcm in size. METHODS: National study including all patients with nonmetastatic A-NET diagnosed after January, 2010 in France. RESULTS: In all, 403 patients were included. A-NETs were: within tip (67%), body (24%) or base (9%) of the appendix; tumor size was <â1âcm (62%), 1 to 2âcm (30%), or >2âcm (8%); grade 1 (91%); mesoappendix involvement 3âmm (5%); lymphovascular (15%) or perineural (24%) invasion; and positive resection margin (8%). According to the European NeuroEndocrine Tumor Society (ENETS) recommendations, 85 patients (21%) should have undergone RHC. The agreement between ENETS guidelines and the multidisciplinary tumor board for complementary RHC was 89%. In all, 100 (25%) patients underwent RHC with LN resection, 26 of whom had LN+. Tumor size (best cut-off at 1.95âcm), lymphovascular and perineural invasion, and pT classifications were associated with LN+. Among the 44 patients who underwent RHC for a tumor of 1 to 2âcm in size, 8 (18%) had LN+. No predictive factor of LN+ (base, resection margins, grade, mesoappendix, lymphovascular, perineural involvement) was found in this subgroup of patients. CONCLUSIONS: In the largest study using the latest pathological criteria for completion RHC in A-NET, a quarter of patients had residual tumor. Further studies are warranted to demonstrate the survival impact of RHC in this setting.
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Apendicectomia , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Colectomia , Linfonodos/patologia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: Data on the diagnostic value of 18F-FDOPA PET/CT in patients with insulinoma are limited and are focused on small patient populations explored using different PET/CT protocols and the inconsistent use of carbidopa premedication. The aim of this study was to improve the current knowledge about the diagnostic value of 18F-FDOPA PET/CT combined with oral carbidopa premedication and early pancreatic imaging for tumour localization in patients with insulinoma-related hyperinsulinaemic hypoglycaemia (HH). The relationships among 18F-FDOPA quantitative uptake parameters, insulin secretion and tumour pathological features were also investigated. METHODS: Of 34 patients with suspicion of insulinoma-related HH examined by dual time-point carbidopa-assisted 18F-FDOPA PET/CT, 24 with histologically proven insulinoma were retrospectively included. One patient underwent two PET/CT examinations for relapsing insulinoma after surgical excision. Thus, 25 preoperative 18F-FDOPA PET/CT studies were finally retained and analysed. All studies were performed under carbidopa premedication (200 mg orally, 1-2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after 18F-FDOPA injection) over the upper abdomen and a delayed whole-body acquisition starting 20-30 min later. The cytological and/or histopathological diagnosis of insulinoma was the diagnostic standard of truth. RESULTS: 18F-FDOPA PET/CT localized insulinoma in 21 of the 25 studies, leading to a primary lesion detection rate of 84%. Four lesions (19%) were detected only on early acquisitions. The false-negative tumour detection rates were, respectively, 22% and 12.5% in patients receiving and not receiving treatment for hypoglycaemic symptoms at the time of PET/CT. In benign insulinomas, the early maximum standardized uptake value (SUVmax) was significantly higher than the delayed SUVmax. Compared to the 21 benign lesions, four malignant insulinomas showed significantly higher 18F-FDOPA uptake. Lesion size, fasting-end insulin and C-peptide levels correlated with tumour 18F-FDOPA uptake, dopaminergic tumour volume and metabolic burden. CONCLUSION: The present study showed that 18F-FDOPA PET/CT combined with carbidopa premedication and early pancreatic acquisitions is a valuable diagnostic option in patients with insulinoma when GLP1R-based imaging is not available. The results also provide new insights into the relationships between tumour secretion and imaging phenotype in insulinomas.
Assuntos
Carbidopa/farmacologia , Di-Hidroxifenilalanina/análogos & derivados , Insulinoma/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Insulina/metabolismo , Insulinoma/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: This study evaluates the impact of macrovascular venous invasion (MVI) on surgical and survival outcomes of pancreatic neuroendocrine tumours (PNETs). METHODS: We retrospectively reviewed data of 125 patients operated for PNETs. Operative, pathological,and survival outcomes were compared between PNETs with and without MVI. RESULTS: Macrovascular venous invasion was detected in 25 of 125 PNETs (20%) presenting as tumour thrombi (n = 12) or venous wall invasion (n = 13). MVI was associated with larger tumours, a higher rate of lymph node involvement, less differentiated tumours, and a higher rate of perineural invasion. Resection of PNETS with MVI more often necessitated combined hepatic, venous and multivisceral resections, had a higher rate of intraoperative blood transfusion (p = 0.04) but similar morbidity (44% vs. 42%) and mortality (0 vs. 1%) as PNETs without MVI. PNETs with MVI had a lower median overall survival rate (60 vs. 149 months; p = 0.03). Multivariate analysis revealed that PNETs of the pancreatic head, synchronous liver metastases and higher tumour grade were prognostic factors for overall survival. CONCLUSIONS: MVI is found in more advanced PNETs. Resection of PNETs with MVI is characterized by increased transfusion rate and reduced overall survival.
Assuntos
Tumores Neuroendócrinos/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Neoplasias Vasculares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Neoplasias Vasculares/mortalidade , Neoplasias Vasculares/cirurgia , Adulto JovemAssuntos
Neoplasias das Glândulas Suprarrenais , Carcinoma de Células Renais , Neoplasias Renais , Feocromocitoma , Neoplasias Cutâneas , Neoplasias Uterinas , Humanos , Feminino , Feocromocitoma/diagnóstico por imagem , Fumarato Hidratase/genética , Mutação em Linhagem Germinativa , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias Cutâneas/patologiaRESUMO
PURPOSE: Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of 18F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up. METHODS: Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated. Patients underwent both 18F-FDOPA PET/CT and MRA (15 patents) or CTA (1 patent). Both methods were first assessed under blinded conditions and afterwards correlated. Head and neck imaging abnormalities without histological confirmation were considered true-positive results based on a consensus between radiologists and nuclear physicians and on further 18F-FDOPA PET/CT and/or MRA. RESULTS: 18F-FDOPA PET/CT and MRA/CTA were concordant in 14 patients and in disagreement in 2 patients. 18F-FDOPA PET/CT and MRA/CTA identified, respectively, 12 and 10 presumed recurrent HNPGLs in 12 patients. The two lesions diagnosed by PET/CT only were confirmed during follow-up by otoscopic examination and MRA performed 29 and 17 months later. 18F-FDOPA PET/CT images were only slightly influenced by the posttreatment sequelae, showing a better interobserver reproducibility than MRA/CTA. Finally, in 2 of the 16 studied patients, 18F-FDOPA PET/CT detected two additional synchronous primary HNPGLs. CONCLUSION: 18F-FDOPA PET/CT is highly sensitive in posttreatment evaluation of patients with HNPGLs, and also offers better interobserver reproducibility than MRA/CTA and whole-body examination. We therefore suggest that 18F-FDOPA PET/CT is performed as the first diagnostic imaging modality in symptomatic patients with suspicion of HNPGL relapse after primary treatment when 68Ga-labeled somatostatin analogues are not available.
Assuntos
Angiografia por Tomografia Computadorizada , Di-Hidroxifenilalanina/análogos & derivados , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imageamento por Ressonância Magnética , Paraganglioma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Di-Hidroxifenilalanina/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Paraganglioma/metabolismo , Recidiva , Estudos RetrospectivosRESUMO
Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d'étude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families. Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.
Assuntos
Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/mortalidade , Mutação , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas/genética , Família , Feminino , Seguimentos , Humanos , Masculino , Neoplasia Endócrina Múltipla Tipo 1/metabolismo , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fatores de RiscoRESUMO
Everolimus and peptide receptor radionuclide therapy (PRRT, 177Lu-DOTATATE) are 2 treatments recommended in guidelines for gastroenteropancreatic metastatic neuroendocrine tumors. However, the best treatment sequence remains unknown. Methods: We designed a retrospective multicenter study that included patients from the national prospective database of the Groupe d'Étude des Tumeurs Endocrines who had been treated using everolimus and PRRT between April 2004 and October 2022. The primary aim was to compare the 2 treatments (everolimus and PRRT) in terms of efficacy and safety, and the secondary aim was to evaluate the sequences (PRRT followed by everolimus or everolimus followed by PRRT) based on overall progression-free survival (PFS) (PFS during first treatment + PFS during second treatment) in patients with metastatic neuroendocrine tumors. Results: Both treatments were used for 84 patients. The objective response rate and median PFS were 5 mo (6.0%) and 16.1 mo (95% CI, 11.5-20.7 mo), respectively, under everolimus and 19 mo (22.6%) and 24.5 mo (95% CI, 17.7-31.3 mo), respectively, for PRRT. The safety profile was also better for PRRT. Median overall PFS was 43.2 mo (95% CI, 33.7-52.7 mo) for the everolimus-PRRT sequence and 30.6 mo (95% CI, 17.8-43.4 mo) for the PRRT-everolimus sequence (hazard ratio, 0.69; 95% CI, 0.39-1.24; P = 0.22). Conclusion: PRRT was more effective and less toxic than everolimus. Overall PFS was similar between the 2 sequences, suggesting case-by-case discussion if the patient is eligible for both treatments, but PRRT should be used first when an objective response is needed or in frail populations.
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Craniopharyngiomas are rare hypothalamic-pituitary tumors found in young children, adolescents and adults, and their multidisciplinary management required, calls for consistent practices for practicioners, patients and families. The French Endocrine Society and French Society for Pediatric Endocrinology & Diabetes enlisted and coordinated adult and paediatric endocrinologists, neurosurgeons, pathologists, radiotherapists as well as psychologists, dieticians and a patient association, to draft a reference document on this severe disease. The management of craniopharyngiomas remains complex due to their aggressive nature, invasive behavior, and propensity for recurrence, requiring a sequential and measured therapeutic approach and follow-up in expert centers. Although patient survival rates are high, the consequences of both the tumor and its treatment can lead to serious comorbidities and impaired quality of life, particularly in those patients with lesional hypothalamic syndrome. Recent advances have allowed the two described tumor types - papillary and adamantinomatous - to be associated with distinct molecular signatures, specific pathophysiological mechanisms and ipso facto, distinct therapeutic approaches, including innovative medications for hyperphagia, that will continue to evolve. This consensus statement covers all stages in the management of patients with craniopharyngioma, from diagnosis to therapeutic strategies including the long-term follow-up.
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OBJECTIVE: Glucagonoma is a very rare functional pancreatic neuroendocrine tumor (PanNET). We aimed to provide data on the diagnosis, prognosis, and management of patients with glucagonoma. DESIGN AND METHODS: In this retrospective national cohort, we included all patients with glucagonoma, defined by at least 1 major criterion (necrolytic migratory erythema [NME] and/or recent-onset diabetes, and/or weight loss ≥ 5â kg) associated with either glucagonemia > 2 × upper limit of normal or positive glucagon immunostaining. Antisecretory efficacy was defined as partial/complete resolution of glucagonoma symptoms. Antitumor efficacy was assessed according to the time to next treatment (TTNT). RESULTS: Thirty-eight patients were included with median age 58.7 yo, primary PanNET located in the tail (68.4%), synchronous metastases (63.2%). Median Ki-67 index was 3%. Most frequent glucagonoma symptoms at diagnosis were NME (86.8%), weight loss (68.4%), and diabetes (50%). Surgery of the primary PanNET was performed in 76.3% of cases, mainly with curative intent (61.5%). After surgery, complete resolution of NME was seen in 93.8% (n = 15/16). The secretory response rates were 85.7%, 85.7%, 75%, and 60% with surgery of metastases (n = 6/7), chemotherapy (n = 6/7), liver-directed therapy (n = 6/8), and somatostatin analogs (n = 6/10), respectively. All lines combined, longer TTNT was reported with chemotherapy (20.2 months). Median overall survival (OS) was 17.3 years. The Ki-67 index > 3% was associated with shorter OS (hazard ratio 5.27, 95% CI [1.11-24.96], P = .036). CONCLUSION: Patients with glucagonoma had prolonged survival, even in the presence of metastases at diagnosis. Curative-intent surgery should always be considered. Chemotherapy, peptide receptor radionuclide therapy, or liver-directed therapy seems to provide both substantial antitumor and antisecretory efficacies.